Logo do repositório
 
Publicação

Adenosine A2A receptors enhance GABA transport into nerve terminals by restraining PKC inhibition of GAT-1

2009Artigo científico Acesso restrito
Ver registo simples
dc.contributor.authorCristóvão-Ferreira, Sofia
dc.contributor.authorVaz, Sandra H.
dc.contributor.authorRibeiro, Joaquim A.
dc.contributor.authorSebastião, Ana M
dc.date.accessioned2012-05-28T16:10:00Z
dc.date.available2012-05-28T16:10:00Z
dc.date.issued2009
dc.description© 2009 International Society for Neurochemistry © 2009 The Authorseng
dc.descriptionThe definitive version is available at www3.interscience.wiley.com][A versão definitiva está disponível em www3.interscience.wiley.com]eng
dc.description.abstractNeurotransmitter transporters are regulated by phosphorylation but little is known about endogenous substances and receptors that regulate this process. Adenosine is an ubiquitous neuromodulator operating G-protein coupled receptors, which affect the activity of several kinases. We therefore evaluated the influence of adenosine upon the GABA transporter 1 (GAT-1) mediated GABA uptake into hippocampal synaptosomes. Removal of endogenous adenosine (adenosine deaminase, 1 U/mL) decreased GABA uptake, an effect mimicked by blockade of A2A receptors (2-(2-furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, 50 nM) but not A1 or A2B receptors. A2A receptor activation (4-[2-[[6-amino-9-(N-ethyl-b-D-ribofuranuronamidosyl)- 9H-purin-yl]amino]ethyl]benzenepropanoic acid hydrochloride, 3–100 nM) enhanced GABA uptake by increasing the transporter Vmax without change of KM. This was mimicked by adenylate cyclase activation (forskolin, 10 lM) and prevented by protein kinase A (PKA) inhibition (N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide dihydrochloride, 1 lM), which per se did not influenceGABAtransport. Blockade of protein kinase C (PKC) (2-[1-(3-dimethylaminopropyl)indol- 3-yl]-3-(indol-3-yl) maleimide, 1 lM) facilitated GABA transport whereas PKC activation (4-b-phorbol-didecanoate, 250 nM) inhibited it. PKA blockade did not affect the facilitatory action of the PKC inhibitor or the inhibitory action of the PKC activator. However, when adenylate cyclase was activated neither activation nor inhibition of PKC affected GABA uptake. It is concluded that A2A receptors, through activation of the adenylate cyclase/cAMP/PKA transducing pathway facilitate GAT-1 mediated GABA transport into nerve endings by restraining tonic PKC-mediated inhibition.eng
dc.description.sponsorshipWork supported by Fundação para a Ciência e Tecnologia (FCT)and European Union (Cost B30 concerted action). SCF and SHVare in recipient of FCT fellowships SFRH/BD/38099/2007 and SFRHBD/27989/2006). The animal housing facilities of the Institute of Physiology of the Faculty of Medicine of Lisbon are also acknowledged.eng
dc.identifier.citationJournal of Neurochemistry | 2009 | 109 | 336–347por
dc.identifier.issn0022-3042
dc.identifier.urihttp://hdl.handle.net/10451/6378
dc.identifier.uridoi: 10.1111/j.1471-4159.2009.05963.x
dc.identifier.urihttp://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2009.05963.x/pdf
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherWiley-Blackwellpor
dc.subjectA2A receptorseng
dc.subjectAdenosineeng
dc.subjectGABA transporteng
dc.subjectGABA transporter 1eng
dc.subjectProtein kinase Aeng
dc.subjectProtein kinase Ceng
dc.titleAdenosine A2A receptors enhance GABA transport into nerve terminals by restraining PKC inhibition of GAT-1eng
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage347por
oaire.citation.startPage336por
oaire.citation.titleJournal of Neurochemistryeng
person.familyNameSebastião
person.givenNameAna M
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.orcid0000-0001-9030-6115
person.identifier.scopus-author-id7004409879
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublication304abd7f-071b-4447-a8a3-4aa5f0547141
relation.isAuthorOfPublication.latestForDiscovery304abd7f-071b-4447-a8a3-4aa5f0547141

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura indisponível
Nome:
Cristovao_Ferreira_01.pdf
Tamanho:
582.65 KB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

FM-IFN-Artigos em Revistas Internacionais